Zolpidem

Is zolpidem safe?

For a few nights or weeks, at the label dose and with a full night in bed, it is reasonably safe for most adults. Zolpidem, sold as Ambien in the US and Stilnoct in the UK, helps people fall asleep and is cleared within hours, with a half-life of about 2.5 hours.

The problem is that its rare harms are severe and it is easy to use it in the riskiest ways: longer than intended, with alcohol, or with less than a full night's sleep ahead. It carries a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary for sleep-walking and sleep-driving, it is a controlled drugControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary, and next-morning impairment is common enough that the doses were cut. We score it 53, above alprazolam at 40 and below pregabalin at 57.

Sleep-driving and other complex sleep behaviours

In April 2019 the FDA added its strongest warning to zolpidem, eszopiclone and zaleplon. Its review found 66 cases of complex sleep behaviours that led to serious injury, including deaths; 61 involved zolpidem, which reflects how much more often it is prescribed. Reported injuries included falls, burns, near-drowning, carbon monoxide poisoning and hypothermia.

These episodes can happen after the first dose or after months, at recommended doses and without alcohol. People usually remember nothing. Activities reported on the label include walking, driving, preparing and eating food, making phone calls and having sex. Anyone who has had an episode should not take zolpidem again; the label lists that as a contraindicationContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary.

Next-day impairment

Zolpidem's blood levels can still be high enough to impair driving the morning after, especially in women, who clear it more slowly. That is why the US label starts women on 5 mg (and 6.25 mg for Ambien CR) and allows men 5 or 10 mg, with an absolute ceiling of 10 mg a night (12.5 mg for the CR form).

Rule from the label and the MHRA	Why
Take it right before bed with 7 to 8 hours to sleep	Shorter nights leave more drug in the blood
One dose a night only, never re-dose	Second doses raise morning levels
No driving or machinery for at least 8 hours (MHRA)	Reaction time and alertness can be impaired
No alcohol or other sedatives	Additive sedation and complex behaviours
5 mg for older adults and mild to moderate liver disease	Higher levels and more falls

Older people are at particular risk of night-time falls, which the label flags. Many guidelines advise avoiding sleeping pills in this group where possible.

Dependence and stopping

Zolpidem is a Schedule IVControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary controlled substance, like benzodiazepines. In studies of people with a history of drug misuse, 40 mg produced effects similar to 20 mg of diazepam, though the normal 10 mg dose was hard to tell from placebo. The label says the risk of dependence rises with dose and length of treatment, that long-term use is not recommended, and that insomnia lasting beyond 7 to 10 days of treatment should prompt a fresh look for an underlying cause.

After regular use, stopping suddenly can bring withdrawal symptoms, according to the label. A gradual reduction planned with the prescriber is the safer route. For long-term insomnia, cognitive behavioural therapy for insomnia (CBT-I) is the first-line treatment in most guidelines and carries none of these risks.

Interactions and overdose

The dangerous combinations are with other depressants of the brain and breathing:

• alcohol, which worsens sedation, memory gaps and complex sleep behaviours
• opioids such as oxycodone or codeine, which add breathing depression
• benzodiazepines, other sleeping pills, gabapentin or pregabalin, and sedating antidepressants and antihistamines

Ketoconazole and other strong CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors raise zolpidem levels; rifampin and St John's wort reduce its effect. The label reports fatal overdoses with zolpidem alone or combined with other depressants. If someone has taken too much, especially with alcohol or opioids, call 911 in the US (Poison Help on 1-800-222-1222) or 999 in the UK.

Who should be careful

Talk to your doctor or pharmacist before taking zolpidem if you are over 65, have sleep apnoea, COPD or other breathing problems, liver disease, depression or a history of drug or alcohol misuse, or take an opioid, a benzodiazepine or any other sedative. Plan never to take it unless you can stay in bed for a full night.

How we scored it

Track record (88) is the only strong factor. Regulatory warnings (30) reflect the 2019 boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and contraindicationContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary, and interactions (40) and dependence (42) the controlled status and the risks with alcohol, opioids and other sedatives. Serious side effects (55) balance mild everyday effects against rare but grave complex sleep behaviours.